Cell-Stress-Free Percutaneous Bioelectrodes

Abstract

Wearable bioelectronics have advanced dramatically over the past decade, yet remain constrained by their superficial placement on the skin, which renders them vulnerable to environmental fluctuations and mechanical instability. Existing microneedle (MN) electrodes offer minimally invasive access to dermal tissue, but their rigid, bulky design-often 100 times larger and 10,000 times stiffer than dermal fibroblasts-induces pain, tissue damage, and chronic inflammation, limiting their long-term applicability. Here, a cell-stress-free percutaneous bioelectrode is presented, comprising an ultrathin (<2 µm), soft MN (sMN) that dynamically softens via an effervescent structural transformation after insertion. The sMN exhibits near-zero Poisson's ratio deformation, preserving cellular morphology and minimizing immune activation over multiple days of use in rats and humans. Synchrotron imaging and histological analysis reveal reduced tissue disruption, while electrophysiological measurements demonstrate stable signal-to-noise ratios under sweat, dehydration, and extended use. This architecture shifts the biosensing interface from the epidermis to the dermis, establishing a mechanically and electrically stable platform for environment-independent signal acquisition. The findings establish dermal electronics as a next-generation paradigm for long-term, biocompatible wearable sensing.

Keywords: cell stress; microneedle; on‐skin bioelectrode; percutaneous; soft electronics.

Figure 1

Mechanism of action and tissue compatibility of the cell‐stress‐free percutaneous bioelectrode. a), Schematic illustration of the effervescent transformation of the soft microneedle (sMN) bioelectrode. Before effervescence, the sMN—composed of polyvinylpyrrolidone (PVP), citric acid, and sodium bicarbonate—penetrates the skin while exerting transient mechanical stress, as indicated by localized red shading. When a small amount of water is applied, an effervescent reaction occurs, producing CO₂ bubbles and dissolving the sacrificial matrix. As the reactive components vanish, the surrounding skin partially closes, leaving only the ultrathin parylene–gold–parylene film electrode in place. The process completes with the skin pores fully closed and the flexible sMN conformally integrated with the tissue, minimizing residual stress. b,c), Hematoxylin and eosin (H&E)–stained cross‐sections of Sprague–Dawley (SD) skin with bMN (b) and sMN (c) insertions. The bMN causes noticeable tissue deformation, whereas the sMN conforms with minimal disruption. A nearby hair follicle of similar size and shape is visible in the section. d–g), Schematic of cell–microneedle interactions. Cells initially maintain a stable shape with intact phospholipid bilayers (d). A rigid MN compresses cells, deforming and destabilizing their membranes (e), which can lead to bilayer disruption and damage under sustained stress (f). When the MN softens rapidly, cells recover their shape and membrane integrity, allowing the sMN to settle between cells without further damage (g).

Figure 2

Mechanical transformation and durability of the sMN bioelectrode. a), Schematic and optical images showing that bMN fractures under shear force (top), whereas post‐effervescence (softened) sMN undergoes elastic buckling without damage (bottom). b), Photographs before and after effervescence, illustrating the transition from a rigid patch to an ultrathin, flexible sMN. c), Comparison of the effective Young's modulus of bMN, skin tissue, and softened sMN, showing that the sMN achieves a significantly lower modulus (34.5–27.8 MPa) than bMN (3.6–3.9 GPa), enabling superior mechanical compliance (Left). Load–displacement curves under three shear cycles, where bMN fails on the first cycle while sMN remains stable (Middle). Impedance of sMN at 100 Hz–100 kHz after 0–1000 bending cycles, showing negligible electrical change (Right).

Figure 3

Mechanical adaptability of and deformation behavior of bMN and sMN. a), Synchrotron X‐ray images of bMN (top) and sMN (bottom) under negative, zero, and positive curvature of rat skin, with insets showing patch conformality. bMN fractures or detaches under compression or tension, while sMN maintains conformal contact, compressing or spreading laterally as needed. b), 3D synchrotron micro‐CT rendering of sMN with intensity‐based colormap, illustrating flexible deformation inside tissue. c), Cross‐sectional area analysis along insertion depth, where bMN shows a steady taper, whereas sMN exhibits variable expansion and contraction (maximum planar deformation ≈46%). d, Trajectory of the centroids along the MN axis, showing lateral displacement of sMN and bMN (left). Quantified total lateral displacement, highlighting ≈9 times higher adaptability of sMN compared to bMN (right).

Figure 4

Human‐subject evaluation of discomfort and skin irritation after electrode use. a), Visual analogue scale (VAS) scores from participants reporting discomfort associated with four types of electrodes: bMN, fMN, sMN, and thin‐film. b), Representative images of the skin before and immediately after detachment of the device, taken one week after initial application. Yellow dashed boxes indicate device location; yellow arrows mark residual micropores. c), Quantification of skin redness over 7 days, normalized to the baseline level measured at day 0, where all groups (bMN, fMN, and sMN) exhibited comparable redness. d) Micro pore closure rates were analyzed using one‐way ANOVA. Results are presented as mean ± s.d., with n = 8 per group, which shows the statistical significance between groups (Thin film, sMN, fMN, bMN) using significance markers (^* p < 0.05, ^** p < 0.01, ^*** p < 0.001, see Tables S2 and S3, Supporting Information).

Figure 5

Histological mapping and quantitative analysis of inflammation induced by different percutaneous platforms. a), H&E‐stained tissue sections of SD rat skin implanted with sMN, fMN, bMN, or a 26G medical syringe, collected on days 1, 2, and 4 post‐insertion. Inflammation severity was visualized using 5‐level colormap overlays to highlight immune cell distribution around the insertion sites. b), Quantitative inflammatory cell counts plotted as a function of distance from the device–tissue interface. Dashed line indicates the threshold for “non‐inflammatory regime” (<0.2 cells per 196 µm²).

Figure 6

Long‐term and environment independent electrophysiological signal monitoring using sMN electrodes. a), Equivalent circuit model of the skin–electrode interface. The epidermis introduces variable impedance; the dermis maintains stable electrical properties. b), Block diagram of the EMG signal acquisition system. c), EMG waveforms recorded using sMN (top), film (middle), and gel (bottom) electrodes under wet and dry skin conditions. d), Longitudinal EMG recordings from each electrode type over 7 days. e), Relative SNR (%) of each electrode over time, rescaled to day 0 baseline.